BACKGROUND: The pathogenesis of inflammation in eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS) remains poorly understood. This study aimed to assess immune cell infiltration within the sinonasal microenvironment in these conditions. METHODS: A prospective case-controlled study was conducted to evaluate the expression of CD3, CD11b, CD16, and CD19 in CRS. Sinonasal mucosal sections from patients with ECRS (n = 18), NECRS (n = 27), and normal controls (n = 12) were analyzed by immunohistochemistry. Preoperative clinical data, including sinonasal symptoms, allergy and asthma status, endoscopic Lund‒Kennedy score, radiological Lund‒Mackay score, and peripheral blood morphological parameters, were collected. Expression profiles were then correlated with clinical data. RESULTS: Significant differences were observed in the number of CD11b-positive and CD19-positive cells between ECRS and NECRS patients, as well as in the number of CD3-positive cells in CRS groups compared to controls. In ECRS patients, a positive correlation was found between the expression of CD16-positive and CD11b-positive cells. Additionally, elevated B-cell expression in this group was associated with olfactory dysfunction and the radiological severity of lesions. CONCLUSION: Our study reveals distinct inflammatory patterns in ECRS and NECRS and provides new insights into the underlying mechanisms of CRS. The assessment of CD11b, CD16, and CD19 expression could potentially serve as biomarkers to predict treatment response, especially in patients undergoing monoclonal antibody therapy.